Tramadol hydrochloride and acetaminophen

Uses

Physicians order tramadol hydrochloride and acetaminophen preparations for the short-term relief of acute pain expected to last five days or less. Tramadol hydrochloride and acetaminophen is for adults.

General Drug Information

Janssen Ortho LLC combines 37.5 mg of tramadol hydrochloride and 325 mg of acetaminophen into the name brand tablet, ULTRACET. Several pharmaceutical companies offer ULTRACET in the United States, including Janssen Pharmaceuticals, Ortho-McNeil Pharmaceuticals and Quality Care Products; this product is known as Tramacet in Canada.

Administration/Dosage

Tramadol hydrochloride and acetaminophen is available in tablet form for oral use. The typical dose is two tablets every 4 - 6 hours as necessary to control pain. Patients should never exceed eight tablets in any 24-hour period.

Elderly patients over the age of 65 may be more sensitive to the effects of tramadol and require smaller doses. Those with certain types of kidney problems should not take more than two tramadol hydrochloride and acetaminophen tablets in any 12-hour period.

Tramadol hydrochloride and acetaminophen is for short-term therapy not expected to last more than five days.

Action

Tramadol hydrochloride and acetaminophen work in different ways to provide complete pain relief.

The liver metabolizes tramadol hydrochloride and acetaminophen into smaller components; the kidneys flush these metabolites from the system in urine. Liver or kidney dysfunction can affect the action of tramadol hydrochloride and acetaminophen.

Tramadol Hydrochloride

Tramadol dulls the brain’s perception of pain by depressing the central nervous system, or CNS. This CNS depression also causes sedation and a pleasant euphoric feeling. Opioids such as tramadol also depress respiratory centers to slow breathing.

In a separate action, tramadol changes the way the body reabsorbs serotonin, a hormone associated with mood, learning and sleep. Tramadol inhibits the reuptake of serotonin to cause high levels of this hormone.

Acetaminophen

Acetaminophen prohibits the production of prostaglandin, a hormone responsible for sending pain messages to the brain and increasing body temperature.

Warnings

Hepatotoxicity

Doctors have reported hepatotoxicity, or liver damage caused by medications, in patients who have used acetaminophen. Hepatotoxicity can sometimes result in liver transplant and death. This form of liver disease is usually associated with high doses of acetaminophen, usually exceeding 4,000 mg in a 24-hour period. Patients with underlying liver disease and those who consume alcohol while taking tramadol hydrochloride and acetaminophen are at higher risk for developing hepatotoxicity.

Hepatotoxicity is often the result of taking multiple products containing acetaminophen. In many cases, the patient did not know how much acetaminophen he had taken as this analgesic is a common ingredient in many prescription and over-the-counter products. Prescribing physicians should instruct patients to read the labels of all prescription and non-prescription medications and total the acetaminophen content. Drug makers may refer to acetaminophen as APAP or by its brand name, Tylenol.

Someone who has consumed more than 4,000 mg of acetaminophen in any 24-hour period should seek medical attention, even if she feels well - signs and symptoms of an acetaminophen dose large enough to cause hepatotoxicity may not appear for two to three days.

Respiratory Depression

Tramadol hydrochloride depresses respiratory centers in the brain. This respiratory depression causes slow, shallow breathing patterns that prevent the lungs from effectively exchanging spent carbon dioxide for fresh oxygen, resulting in oxygen starvation and high levels of carbon dioxide. Respiratory depression can be fatal; attendants should treat respiratory depression as a drug overdose.

Prescribers should consider a non-opioid pain reliever for patients at high risk for respiratory depression, including elderly patients and those with significant pre-existing breathing problems.

Serotonin Syndrome

Tramadol inhibits the reuptake of serotonin; this reuptake inhibition may cause serotonin to rise to dangerous levels. Toxic levels of serotonin may result in serotonin syndrome, a potentially fatal condition.

Symptoms of serotonin syndrome include changes in mental status, such as agitation, hallucinations and coma. Other symptoms include rapid pulse, fluctuations in blood pressure and high body temperature. A patient experiencing serotonin syndrome may suffer a lack of coordination, nausea, vomiting and diarrhea.

Combining tramadol with other drugs that inhibit serotonin reuptake increases the risk for serotonin syndrome, even at recommended doses. Examples of other drugs that do this are the popular antidepressant and blood pressure medications known as MAOIs and selective serotonin reuptake inhibitors, or SSRIs. The antidepressant medication TCA and the migraine remedy, triptan, also inhibit serotonin reuptake.

Some medications interfere with the way the liver metabolizes tramadol hydrochloride, causing tramadol to accumulate in the body. High levels of tramadol may cause serotonin syndrome. Examples of drugs that do this are CYP2D6 and CYP3A4 inhibitors.

Seizure Risk

Tramadol may cause seizures. While high doses of tramadol hydrochloride and acetaminophen increase the risk for seizures, a patient may suffer convulsions even at therapeutic doses. Taking tramadol hydrochloride along with certain other medications increase the risk for seizures.

Allergic and Anaphylactic Reactions

Individuals with a known hypersensitivity to tramadol hydrochloride, acetaminophen or other opioids should not use this combination product.

It is possible to suffer an allergic or anaphylactic reaction to either tramadol hydrochloride or acetaminophen. Someone having an allergic reaction to tramadol hydrochloride can experience hives, rash, itching, wheezing, swelling and serious, sometimes life threatening fatal skin reactions. Symptoms of an allergic reaction to acetaminophen include swelling of the face, mouth or throat. Other symptoms of an acetaminophen allergy include breathing problems, itchy hives or rash, and vomiting.

Anaphylaxis is a severe form of an allergic reaction that can sometimes be fatal. Unlike an allergic reaction, an anaphylactic reaction can occur the first time the patient takes tramadol hydrochloride and acetaminophen. In fact, most cases of an anaphylactic response to tramadol hydrochloride and acetaminophen occur with the first dose.

Use in Patients with Head Injury and Increased Intracranial Pressure

Inadequate lung function associated with respiratory depression raises carbon dioxide levels and increases the intracranial fluid pressure surrounding the patient’s brain. Head injuries and pre-existing high intracranial pressure can enhance these effects to cause even higher levels of carbon dioxide and intracranial pressure.

Tramadol hydrochloride and acetaminophen effects can mimic those of a head injury; tramadol hydrochloride and acetaminophen products can obscure the presence and healing process of head injuries.

Suicide Risk

Tramadol hydrochloride and acetaminophen use increases a patient’s risk for suicide. Doctors should prescribe tramadol hydrochloride and acetaminophen products with care to suicidal patients and to those prone to drug addiction. Tramadol has been associated with deaths in patients with a history of emotional disturbances, suicide attempts or suicidal thoughts, or alcohol or drug abuse.

Dependence

Anyone who uses opioids such as tramadol regularly for more than a few weeks can become physically dependent on this class of drugs. An opioid-dependent person suffers uncomfortable withdrawal symptoms when he discontinues tramadol suddenly.

Precautions

Tramadol hydrochloride and acetaminophen can interfere with the consumer’s physical and mental abilities. Patients should not drive a motor vehicle or operate other heavy machinery until they know how tramadol affects them.

Contraindications

Tramadol hydrochloride and acetaminophen products are not suitable for everyone. Tramadol is not appropriate in any circumstance where opioids are not safe, especially in cases of respiratory depression outside of monitored settings or in locations without oxygen and resuscitative equipment.

Patients suffering from acute alcohol or drug intoxication should not use tramadol hydrochloride and acetaminophen products. Tramadol may worsen central nervous system and respiratory depression in these patients.

Pregnancy, Labor and Delivery, Breastfeeding

The FDA categorizes tramadol hydrochloride and acetaminophen as , as scientists cannot rule out the possibility that this drug poses a risk to a pregnant woman or fetus, or to male or female reproductive capabilities. A pregnant woman should take tramadol hydrochloride and acetaminophen only when the benefits to the mother’s health clearly outweigh the possible risks.

A baby born to a woman who takes tramadol hydrochloride and acetaminophen during pregnancy may suffer withdrawal symptoms or seizures after delivery. The baby may be stillborn or die after delivery.

Tramadol hydrochloride and acetaminophen may pass from the mother to the baby through breast milk. Women who need pain relief should ask for another form of analgesia or discontinue breastfeeding.

Drug Interactions

Tramadol hydrochloride and acetaminophen can interact with other medications to produce dangerous or unintended results.

When combined with tramadol hydrochloride and acetaminophen, CYP2D6 and CYP3A4 inhibitors increase the risk for serotonin syndrome.

Taking ULTRACET along with the drugs known as increases the risk for serotonin syndrome. Drugs in these classes include heart-rhythm drug quinidine, the antibiotic erythromycin, and the active ingredients in the mood-altering drugs Prozac, Paxil and amitriptyline. Quinidine may also increase the concentration of tramadol in the blood.

The active ingredient in the anti-seizure drug Tegretol, carbamazepine, increases the metabolism of tramadol and therefore reduces its analgesic effects. Furthermore, tramadol increases the likelihood of seizures in patients with a history of convulsion.

Side effects

All drugs, including tramadol hydrochloride and acetaminophen, may cause adverse reactions in some patients. Consumers most commonly reported constipation, drowsiness, sweating, diarrhea, nausea and loss of appetite, dizziness and itching. Serious side effects include respiratory depression, serotonin syndrome and seizures.

Overdose

Someone can overdose on either the tramadol hydrochloride or the acetaminophen components of this combination product, or both. Overdose of either tramadol hydrochloride or acetaminophen is a serious and sometimes fatal condition.

Nearly lose their lives each year to prescription drug overdose. Tramadol overdose may also cause respiratory depression, lethargy, unconsciousness, seizures, and stopped heartbeat. Someone who has taken a tramadol overdose may be extremely sleepy and fall into a coma, or have limp muscles and cold, clammy skin. His pulse may slow and his blood pressure may drop.

It is possible to overdose on acetaminophen; it is one of the worldwide. In the United States, about 60,000 people suffer from acetaminophen overdose each year. Acetaminophen overdose is the among Americans. Acetaminophen overdose can also cause kidney problems, low blood sugar and blood clotting problems that lead to uncontrolled bleeding.

Early symptoms of tramadol hydrochloride overdose include respiratory depression or seizures. Early symptoms of an acetaminophen overdose include loss of appetite, nausea and vomiting, lack of energy, pale skin and extreme perspiration. Laboratory tests and physical examination may not reveal acute liver damage for up to 48 to 72 hours after a hepatotoxic dose of acetaminophen.

Workers may slide a flexible tube into the victim’s throat to hold his airway open; they may attach this tube to a mechanical ventilator that breathes for the patient. Nurses introduce activated charcoal into the patient’s stomach to absorb excess medication. If only a few hours have passed since the ingestion of a hepatotoxic dose, nurses will administer the antidote to acetaminophen, N-acetylcysteine. If the patient shows signs of respiratory depression, doctors will order naloxone. While naloxone reverses respiratory depression, it can also cause seizures.

Abusing tramadol hydrochloride and acetaminophen increases the risk for overdose and death.

Abuse

Tramadol produces a pleasant euphoria, making it a target for recreational drug users. Abusing tramadol hydrochloride and acetaminophen increases the risk for adverse reactions, toxic overdose, addiction or physical dependence.

Withdrawal

An opioid-dependent person suffers withdrawal symptoms when he stops using tramadol suddenly. The human body grows accustomed to high levels of toxic chemicals including tramadol; when tramadol levels drop rapidly, the body struggles to adapt to this sudden detoxification.

Withdrawal symptoms begin a few hours after the last dose of tramadol hydrochloride. These symptoms last for five or more days. Without intervention, these symptoms fade as the detoxification process completes ; withdrawal symptoms do not return unless the patient once again become opioid-dependent. The individual can stop withdrawal symptoms at any time by taking more tramadol, but relapsing to opioid use halts the detoxification process and leaves the individual still dependent on opioids.

Doctors suggest patients avoid withdrawal symptoms by taking smaller doses further apart. This tapering method works well for most people but a large number of individuals cannot overcome persistent and severe withdrawal symptoms. According to the , there are nearly 2 million opioid-dependent people living in the United States.

Detox

Hospitals and local healthcare institutions help individuals overcome opioid-dependence through detoxification services. During detoxification, patients receive medications to initiate the detoxification process along with medications that soothe withdrawal symptoms. These medically assisted detoxification programs ease the severity of withdrawal symptoms but does not shorten the detoxification process.

Many informed patients now choose rapid detox. During humane and efficient rapid detox procedures, doctors sedate and anesthetize patients before administering the standard detoxification and anti-withdrawal drugs so that patients rest in a comfortable “twilight sleep” during the difficult detoxification process. Patients awaken a few hours later, renewed and refreshed.

Storage

Consumers and healthcare professionals should store tramadol hydrochloride and acetaminophen at 77 degrees Fahrenheit but this combination drug can tolerate temperatures ranging from 59 to 86 degrees.

Miscellaneous information

Tramadol hydrochloride and acetaminophen tablets are light yellow in color, coated and shaped like a capsule. The initials “O-M” appear on one side of the tablet and the number 650 is on the other side.